EP0126894B1 - Troponon-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzung - Google Patents

Troponon-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzung Download PDF

Info

Publication number
EP0126894B1
EP0126894B1 EP84103454A EP84103454A EP0126894B1 EP 0126894 B1 EP0126894 B1 EP 0126894B1 EP 84103454 A EP84103454 A EP 84103454A EP 84103454 A EP84103454 A EP 84103454A EP 0126894 B1 EP0126894 B1 EP 0126894B1
Authority
EP
European Patent Office
Prior art keywords
compound
salt
methyl
hydroxy
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP84103454A
Other languages
English (en)
French (fr)
Other versions
EP0126894A1 (de
Inventor
Ikuo Ueda
Masayuki Kato
Yoshiharu Kasai
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujisawa Pharmaceutical Co Ltd
Original Assignee
Fujisawa Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd
Priority to AT84103454T priority Critical patent/ATE29133T1/de
Publication of EP0126894A1 publication Critical patent/EP0126894A1/de
Application granted granted Critical
Publication of EP0126894B1 publication Critical patent/EP0126894B1/de
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
    • C07D279/08—1,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to novel tropone derivatives. More particularly, it relates to novel tropone derivatives which have antiinflammatory, analgesic and antirheumatic activities, to process for preparation thereof, to pharmaceutical composition comprising the same.
  • the compounds and compositions can be used therapeutically in the treatment of inflammation, various pains and rheumatism in human being and animals.
  • one object of this invention is to provide novel tropone derivatives which are useful as antiinflammatory, analgesic and antirheumatic agents.
  • Another object of this invention is to provide a process for preparation of said tropone derivatives.
  • a further object of this invention is to provide pharmaceutical composition comprising, as an active ingredient, said tropone derivative.
  • Still further object of this invention is to provide said tropone derivatives for use in the treatment of inflammation, various pains and rheumatism in human being and animals.
  • the object tropone derivatives are novel and can be represented by the following general formula [I]. wherein R 1 is hydrogen or C 1 ⁇ C 6 alkyl,
  • the object compound [I] the following points are to be noted. That is, when R 3 is hydrogen, the object compound can be alternatively represented by its tautomers as shown in the following. wherein R 1 and R 2 are each as defined above.
  • the object compound [I] and its salt can be prepared by the following processes. wherein R 1 , R 2 and R 3 are each as defined above, and
  • R3 is aralkenoyl the alkenoyl moiety having up to 6 C atoms.
  • C 1 ⁇ C 6 alkoxy for R 2 may be methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, pentyloxy or hexyloxy.
  • Suitable examples of halogen for R 2 include chlorine, bromine, iodine and fluorine.
  • a suitable example of aralkenoyl the alkenoyl moiety having up to 6 C atoms for R 3 and may be cinnamoyl.
  • Suitable pharmaceutically acceptable salts of the object compound [I] are conventional non-toxic salts and include e.g. a metal salt such as an alkali metal salt [e.g. sodium salt, potassium salt] and an alkaline earth metal salt [e.g. calcium salt, magnesium salt], an ammonium salt, an organic base salt [e.g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N"-dibenzylethylenediamine salt].
  • a metal salt such as an alkali metal salt [e.g. sodium salt, potassium salt] and an alkaline earth metal salt [e.g. calcium salt, magnesium salt], an ammonium salt, an organic base salt [e.g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N"-dibenzylethylenediamine salt].
  • the object compound [I] and its salt can be prepared by reacting a compound [II] or its reactive derivative at the carboxy group or a salt thereof with a compound [III] or its reactive derivative at the amino group or a salt thereof.
  • Suitable reactive derivatives at the carboxy group of the compound [II] may include e.g. an acid halide, an acid anhydride, an ester and an activated amide.
  • Suitable examples of such reactive derivatives may be an ester such as C 1 ⁇ C 6 alkyl ester [e.g. methyl ester, ethyl ester, propyl ester, hexyl ester] or an activated ester with N-hydroxysuccinimide, N-hydroxyphthalimide or 1-hydroxy-6-chlorobenzotriazole, an acid chloride, an acid azide, a mixed acid anhydride with an acid such as substituted phosphoric acid [e.g. dialkylphosphoric acid, phenyl phosphoric acid], aliphatic carboxylic acid [e.g. pivalic acid, acetic acid, trichloroacetic acid a symmetrical acid anhydride, an activated amide with imidazole, triazole or dimethylpyrazole.
  • an ester such as C 1 ⁇ C 6 alkyl ester [e.g. methyl ester, ethyl ester, propyl ester, hexyl ester
  • Suitable reactive derivatives at the amino group of the compound [III] include conventional ones used in amidation, for example, Schiff's base type imino or its tautomeric enamine type isomer formed by reaction of the compound [III] with a carbonyl compound, a silyl derivative formed by reaction of the compound [III] with a silyl compound such as trimethylsilylacetamide or bis(trimethylsilyl)acetamide and a derivative formed by reaction of the compound [III] with phosphorus trichloride or phosgene.
  • the reactive derivatives of the compounds [II] and [III] can be selected according to the kinds of the compounds [II] and [III], respectively.
  • Suitable salts of the compound [II] and its reactive derivative at the carboxy group may be the same as those exemplified forthe compound [I], and suitable salts of the compound [III] and its reactive derivative at the amino group may include a conventional base addition salt as exemplified for the compound [I] and a conventional acid addition salt [e.g. hydrochloride, hydrobromide, formate, acetate, benzenesulfonate].
  • a conventional base addition salt as exemplified for the compound [I]
  • a conventional acid addition salt e.g. hydrochloride, hydrobromide, formate, acetate, benzenesulfonate.
  • the reaction is preferably carried out in the presence of a conventional condensing agent such as N,N'-dicyclohexylcarbodiimide, N-cyclohexyl-N'-morpholinoethylcarbodiimide, N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide, thionyl chloride, oxalyl chloride, lower alkoxycarbonyl halide [e.g. ethyl chloroformate, isobutyl chloroformate, etc.] or 1-(p-chlorobenzenesulfonyloxy)-6-chloro-1 H-benzotriazole.
  • a conventional condensing agent such as N,N'-dicyclohexylcarbodiimide, N-cyclohexyl-N'-morpholinoethylcarbodiimide, N-ethyl-N'-(3-dimethyla
  • the reaction is usually carried out in a conventional solvent such as water, acetone, dioxane, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, benzene, toluene, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent which does not adversely influence the reaction.
  • a conventional solvent such as water, acetone, dioxane, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, benzene, toluene, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent which does not adversely influence the reaction.
  • hydrophilic solvents may be used in a mixture with water.
  • the reaction may be preferably carried out in the presence of an inorganic or an organic base such as an alkali metal hydroxide [e.g. sodium hydroxide, potassium hydroxide], an alkali metal carbonate [e.g. sodium carbonate, potassium carbonate], an alkali metal bicarbonate [e.g. sodium bicarbonate, potassium bicarbonate], tri(lower)alkylamine [e.g. trimethylamine, triethylamine], pyridine or its derivative [e.g. picoline, lutidine or 4-dimethylaminopyridine].
  • an alkali metal hydroxide e.g. sodium hydroxide, potassium hydroxide
  • an alkali metal carbonate e.g. sodium carbonate, potassium carbonate
  • an alkali metal bicarbonate e.g. sodium bicarbonate, potassium bicarbonate
  • tri(lower)alkylamine e.g. trimethylamine, triethylamine
  • pyridine or its derivative e.g. picoline
  • the reaction is preferably conducted in an inert atmosphere such as a stream of nitrogen gas.
  • the reaction temperature is not critical, and the reaction is usually carried out under cooling, at ambient temperature or under warming or heating.
  • the object compound [lb] and its salt can be prepared by reacting a compound [la] or its salt with a compound [IV] or its reactive derivative at the carboxy group or a salt thereof.
  • Suitable reactive derivatives at the carboxy group of the compound [IV] may be the same as those exemplified for the compound [II].
  • Suitable salts of the compound [IV] may be the same as those exemplified for the compound [I].
  • reaction can be carried out substantially in the same manner as that of Process 1, and therefore the reaction mode and reaction conditions [e.g. condensing agent, base, solvent, reaction temperature] of this process are to be referred to those as explained in Process 1.
  • reaction mode and reaction conditions e.g. condensing agent, base, solvent, reaction temperature
  • the object compound [la] and its salt can be prepared by hydrolyzing the compound [Ib] or its salt.
  • This reaction is usually carried out in the presence of an acid or base.
  • Suitable acid includes e.g. an inorganic acid [e.g. hydrochloric acid, hydrobromic acid, sulfuric acid], an organic acid [e.g. formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzenesulfonic acid, p-toluenesulfonic acid] and an acidic ion exchange resin.
  • an inorganic acid e.g. hydrochloric acid, hydrobromic acid, sulfuric acid
  • an organic acid e.g. formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzenesulfonic acid, p-toluenesulfonic acid
  • an acidic ion exchange resin e.g. an inorganic acid [e.g. hydrochloric acid, hydrobromic acid, sulfuric acid]
  • an organic acid e.g. formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzen
  • Suitable base includes e.g. an inorganic base such as alkali or alkaline earth metal hydroxide or the corresponding carbonate or bicarbonate [e.g. sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, calcium hydroxide, magnesium hydroxide,], ammonium hydroxide; an organic base such as an alkoxide or phenoxide of the above metal [e.g. sodium ethoxide, sodium methoxide, lithium phenoxide], an amine such as mono-, di- or trialkylamine [e.g.
  • an inorganic base such as alkali or alkaline earth metal hydroxide or the corresponding carbonate or bicarbonate
  • an organic base such as an alkoxide or phenoxide of the above metal
  • an amine such as mono-, di- or trialkylamine
  • aniline N-methylaniline, N,N-dimethylaniline
  • a heterocyclic base e.g. pyrrolidine, morpholine, N-methylmorpholine, N-methylpiperidine, N,
  • This reaction is usually carried out in a solvent which does not adversely influence the reaction such as water, hydrophilic solvent such as alcohol [e.g. methanol, ethanol, propanol], acetone, N,N-dimethylformamide, tetrahydrofuran, dioxane, dimethyl sulfoxide or a mixture thereof, and other hydrophobic solvents such as benzene and diethyl ether, may also be used as a solvent.
  • a solvent which does not adversely influence the reaction
  • hydrophilic solvent such as alcohol [e.g. methanol, ethanol, propanol]
  • acetone e.g. methanol, ethanol, propanol]
  • acetone N,N-dimethylformamide
  • tetrahydrofuran dioxane
  • dimethyl sulfoxide or a mixture thereof and other hydrophobic solvents
  • other hydrophobic solvents such as benzene and diethyl ether
  • the reaction temperature is not critical, and the reaction is usually carried out at ambient temperature or under warming or heating.
  • the new tropone derivatives [I] and pharmaceutically acceptable salts thereof possess antiinflammatory, analgesic and antirheumatic activities, and are useful for a therapeutic treatment of inflammation, various pains [e.g. headache, toothache, menorrhalgia] and rheumatism.
  • the compounds according to the present invention can be used in a form of pharmaceutical preparation containing one of said compounds, as an active ingredient, in admixture with a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral or parenteral administration.
  • a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral or parenteral administration.
  • the pharmaceutical preparations may be e.g. capsules, tablets, dragees, granules, solution, suspension or emulsion. If desired, there may be included in the above preparations, auxiliary substances, stabilizing agents, wetting or emulsifying agents, buffers and other commonly used additives.
  • an average single dose of about 0.1 mg, 1 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg and 1000 mg of the compounds according to the present invention may be effective for treating inflammation, various pains and rheumatism.
  • amounts between 0.1 mg/body and about 1,000 mg/body or even more may be administered per day.
  • test compound was orally administered 60 minutes prior tcrthe administration of carrageenin and the swelling in the treated limb was compared with that in the control limb.
  • the test compound was administered in a dose of 10 mg/kg.
  • the crystals that have separated out are collected by filtration, washed with toluene and recrystallized from dimethylformamide to give 4 - hydroxy - 2 - methyl - N - (1 - oxo - 2,4,6 - cycloheptatrien - 2 - yl) - 2H - 1,2 - benzothiazine -3 -carboxamide 1,1-dioxide (0.68 g), m.p. 259 ⁇ 261°C.
  • the crystals that have separated out are collected by filtration and recrystallized from dimethylformamidemethanol to give 4 - hydroxy - 2 - methyl - N - (2 - hydroxy - 1 - oxo - 2,4,6 - cycloheptatrien - 5 - yl) - 2H - 1,2 - benzothiazine - 3 - carboxamide 1,1 - dioxide (0.4 g), m.p. 258-265°C.
  • the crystals that have separated out are collected by filtration and recrystallized from dimethylformamide to give 4 - hydroxy - 2 - methyl - N - (7 - methyoxy - 1 - oxo - 2,4,6 - cycloheptatrien - 2 - yl) - 2H -1,2 - benzothiazine - 3 - carboxamide 1,1 - dioxide (0.7 g), m.p. 243-247°C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Rheumatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Professional, Industrial, Or Sporting Protective Garments (AREA)
  • Measurement Of Force In General (AREA)
  • Footwear And Its Accessory, Manufacturing Method And Apparatuses (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Cosmetics (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (11)

1. Verbindung der Formel:
Figure imgb0030
worin R1 Wasserstoff oder C1―C6 Alkyl ist,
R2 Wasserstoff, Hydroxy, Halogen, C1―C6 Alkyl oder C1―C6 Alkoxy ist, und
R3 Wasserstoff oder Aralkenoyl, wobei der Alkenoylteil bis zu 6 Kohlenstoffatome hat und pharmazeutisch annehmbare Salze davon.
2. Verbindung von Anspruch 1, worin R3 Wasserstoff ist.
3. Verbindung von Anspruch 2, worin R1 C1―C6 Alkyl ist.
4. Verbindung von Anspruch 3, worin R1 Methyl ist.
5. Verbindung von Anspruch 4, worin R2 Wasserstoff ist.
6. Verbindung von Anspruch 5, die Formel 4 - Hydroxy - 2 - methyl - N - (1 - oxo - 2,4,6 - cycloheptatrien - 2 - yl) - 2H - 1,2 - benzothiazin - 3 - carboxamid - 1,1 - dioxid ist.
7. Verbindung von Anspruch 1, worin R3 Aralkenoyl ist, wobei der Alkenoylteil bis zu 6 Kohlenstoffatome hat.
8. Verbindung von Anspruch 7, die N - (1 - oxo - 2,4,6 - cycloheptatrien - 2 - yl) - 2 - methyl - 4 - cinnamoyloxy - 2H - 1,2 - benzothiazin - 3 - carboxamid 1,1 - dioxid ist.
9. Verfahren zur Herstellung einer Verbindung der Formel:
Figure imgb0031
worin R1 Wasserstoff oder C1―C6 Alkyl ist,
R2 Wasserstoff, Hydroxy, Halogen, C1―C6 Alkyl oder C1―C6 Alkoxy ist und
R3 Wasserstoff oder Aralkenoyl ist, wobei der Alkenoylteil bis zu 6 Kohlenstoffatome hat, und annehmbare Salze davon, das umfaßt,
a) Reaktion einer Verbindung der Formel:
Figure imgb0032
oder deren reaktiven Derivats an der Carboxygruppe oder eines Salzes davon mit einer Verbindung der Formel:
Figure imgb0033
oder deren reaktivem Derivat an der Aminogruppe oder einem Salz davon, um eine Verbindung der Formel zu liefern:
Figure imgb0034
oder deren pharmazeutisch annehmbares Salz, wobei in den obigen Formeln R1, R2 und R3 jedes wie oben definiert sind; oder -
b) Reaktion einer Verbindung der Formel:
Figure imgb0035
oder deren Salz mit einer Verbindung der Formel:
Figure imgb0036
oder deren reaktivem Derivat an der Carboxygruppe oder einem Salz davon, um eine Verbindung der Formel zu liefern:
Figure imgb0037
oder deren pharmazeutisch annehmbares Salz, wobei in den obigen Formeln R1 und R2 jedes wie oben definiert sind und
Figure imgb0038
 Aralenoyl ist, wobei der Alkenoylteil bis zu 6 Kohlenstoffatome hat; oder
c) Hydrolyse einer Verbindung der Formel:
Figure imgb0039
oder deren Salz, um eine Verbindung der Formel zu liefern:
Figure imgb0040
oder deren pharmazeutisch annehmbares Salz, wobei in den obigen Formeln R1, R2 und
Figure imgb0041
 jedes wie oben definiert sind.
10. Pharmazeutische Zusammensetzung, umfassend eine Verbindung von Anspruch 1, als einen aktiven Inhaltsstoff, in Verbindung mit einem pharmazeutisch annehmbaren im wesentlichen nicht toxischen Trägermaterial oder Arzneimittelverdünnungsmittel.
11. Verbindungen von Anspruch 1 zur Verwendung als ein Medikament.
EP84103454A 1983-03-31 1984-03-29 Troponon-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzung Expired EP0126894B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT84103454T ATE29133T1 (de) 1983-03-31 1984-03-29 Troponon-derivate, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzung.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP57071/83 1983-03-31
JP58057071A JPS59193879A (ja) 1983-03-31 1983-03-31 トロポン誘導体

Publications (2)

Publication Number Publication Date
EP0126894A1 EP0126894A1 (de) 1984-12-05
EP0126894B1 true EP0126894B1 (de) 1987-08-26

Family

ID=13045214

Family Applications (1)

Application Number Title Priority Date Filing Date
EP84103454A Expired EP0126894B1 (de) 1983-03-31 1984-03-29 Troponon-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzung

Country Status (13)

Country Link
US (1) US4540692A (de)
EP (1) EP0126894B1 (de)
JP (1) JPS59193879A (de)
KR (1) KR840008004A (de)
AT (1) ATE29133T1 (de)
AU (1) AU2587284A (de)
DE (1) DE3465594D1 (de)
DK (1) DK168284A (de)
ES (1) ES531141A0 (de)
FI (1) FI841207A (de)
GR (1) GR81759B (de)
NO (1) NO841274L (de)
ZA (1) ZA841840B (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4623486A (en) * 1985-05-29 1986-11-18 Pfizer Inc. [4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity
US4610982A (en) * 1985-06-03 1986-09-09 Pfizer Inc. Anti-inflammatory benzo- and thieno-1,2-thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor
WO1987006933A1 (en) * 1986-05-16 1987-11-19 Pfizer Inc. Benzothiazine dioxide derivatives

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3591584A (en) * 1968-08-27 1971-07-06 Pfizer Benzothiazine dioxides
US3862319A (en) * 1971-02-09 1975-01-21 Pfizer Benzothiazine dioxides as anti-thromobotic agents
JPS5770888A (en) * 1980-10-18 1982-05-01 Shinichi Ito Benzothiazine derivative, its preparation and medicinal composition

Also Published As

Publication number Publication date
JPS59193879A (ja) 1984-11-02
DK168284A (da) 1984-10-01
US4540692A (en) 1985-09-10
FI841207A0 (fi) 1984-03-27
ZA841840B (en) 1984-10-31
EP0126894A1 (de) 1984-12-05
DE3465594D1 (en) 1987-10-01
KR840008004A (ko) 1984-12-12
GR81759B (de) 1984-12-12
DK168284D0 (da) 1984-03-26
FI841207A (fi) 1984-10-01
AU2587284A (en) 1984-10-04
ATE29133T1 (de) 1987-09-15
ES8507524A1 (es) 1985-09-01
NO841274L (no) 1984-10-01
ES531141A0 (es) 1985-09-01

Similar Documents

Publication Publication Date Title
RU2059637C1 (ru) Гетероциклические производные замещенных 2-ациламино-5-тиазолов, способы их получения, производное замещенного 2-аминотиазола, производные 2-амино-4-фенилтиазола
EP0232740A1 (de) Stickstoffenthaltende kondensierte heterozyklische Verbindungen, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
CA3085457A1 (en) Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
US4742057A (en) Antiallergic thiazole compounds
KR20010030629A (ko) 카르복스아미도티아졸 유도체, 그의 제조방법 및 그를함유하는 약학적 조성물
GB1588166A (en) Nitrogen-containing heterocyclic compounds
HU211680A9 (en) Pyrazolopyridine compounds which have useful pharmaceutical utility
HU179492B (en) Process for producing 1,2,4-thiadiasole derivatives
EP0377457A1 (de) Thiazol-Verbindungen, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, welche diese enthalten
US4438126A (en) Lower alkanoic acid derivatives of 2-oxo-benzoxazolines and aldose reductase inhibiting compositions thereof
EP0262873B1 (de) N-Tetrazolyl-thiazolcarboxamid-Derivate und ihre Anwendung
EP0168005B1 (de) Semicarbazidderivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
IE71192B1 (en) 2,4-pyrimidinedione derivatives and pharmaceutical compositions containing them
EP0144853B1 (de) Semicarbazid-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
NZ188770A (en) Thiazolinylguanidine derivatives and pharmaceutical compositions
US4686227A (en) Imidazoisoquinoline compounds useful as anti-ulcerative agents
EP0126894B1 (de) Troponon-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzung
CA2140006A1 (en) Thiazoline derivatives
HU186975B (en) Process for preparing new triazolo-quinazolone derivatives
EP0115979A1 (de) Derivate von 1H,3H-Pyrrolo(1,2-c)thiazol, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen
US4705787A (en) Quinazolinone derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same
EP1819672A1 (de) Indol-2-karbonsäureamide
FR2461705A1 (fr) Nouveaux derives de 1-(4-aminobenzyl)-2,3-dioxopiperazine et leurs sels d'addition d'acides, a action carcinostatique, et procedes pour les preparer
EP0124384A1 (de) Derivate von orthokondensiertem Pyrrol, verwendbar für die Herstellung von Arzneimitteln und Verfahren zu deren Herstellung
US4563453A (en) Thiazine derivatives, processes for preparation thereof and pharmaceutical composition comprising the same

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

17P Request for examination filed

Effective date: 19850529

17Q First examination report despatched

Effective date: 19860605

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Effective date: 19870826

Ref country code: BE

Effective date: 19870826

Ref country code: AT

Effective date: 19870826

REF Corresponds to:

Ref document number: 29133

Country of ref document: AT

Date of ref document: 19870915

Kind code of ref document: T

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Effective date: 19870831

ET Fr: translation filed
REF Corresponds to:

Ref document number: 3465594

Country of ref document: DE

Date of ref document: 19871001

ITF It: translation for a ep patent filed

Owner name: MODIANO & ASSOCIATI S.R.L.

NLV1 Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19880331

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Effective date: 19890329

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Effective date: 19890331

Ref country code: CH

Effective date: 19890331

GBPC Gb: european patent ceased through non-payment of renewal fee
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 19891130

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19891201

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST